Arylpropionitriles are useful precursors to an important class of chiral arylpropionic acids that are nonsteroidal, antiinflammatory drugs, Tetrahedron, 1986, 42 (15), 4095, J. Org. Chem., 1985, 50, 5370. In most cases, the beneficial properties of these drugs are believed to arise from only one enantiomer and, in some cases, the properties of the other enantiomer are harmful. Thus selective, synthetic routes to nonracemic mixtures of arylpropionitriles or arylpropionic acids are highly desirable.
U.S. Pat. Nos. 3,496,215; 3,496,217; 3,496,218; 3,631,191; 3,655,723; 3,798,256; 3,846,461; 3,847,959; and 3,903,120 describe nonenantioselective alkene hydrocyanation in the presence of low valent, organophosphorous Ni catalysts and, in some cases, Lewis acid promoters. The nickel-catalyzed hydrocyanation of styrene and vinylnapthalene derivatives occurs in a predominantly Markovnikov fashion to generate racemic mixtures of chiral, arylpropionitriles (J. Org. Chem., 1985, 50, 5370; Adv. Catal., 1985, 33, 25-31).
Very few examples of enantioselective, transition-metal-catalyzed alkene hydrocyanations have been documented. Reported enantioselective inductions pertain primarily to the enantioselective hydrocyanation of norbornene derivatives, and only modest product e.e.'s (enantiomeric excesses) have been obtained. The highest e.e. reported for any transition-metal-catalyzed enantioselective alkene hydrocyanation is 40% for a Pd catalyzed hydrocyanation of norbornene (6% product yield; Organometallics 1988, 7, 1761).
To achieve the enantioselective alkene hydrocyanation of the instant invention, Applicants have used a class of nickel hydrocyanation catalyst compositions comprised of zero-valent nickel and chiral, nonracemic bidentate organophosphorus ligands. Such catalysts are not known to have been used previously in enantioselective hydrocyanation of aromatic vinyl compounds.
The use of catalyst compositions of zero-valent nickel and chiral, nonracemic O-substituted, bidentate diolphosphorus ligands derived from chiral diols for the enantioselective hydrocyanation of norbornene have been reported in Aust. J. Chem., 19082, 35, 2069; J. Chem. Soc. Commun., 1991, 1292). However, use of such catalysts on aromatic vinyl substrates is not disclosed.
Nonracemic mixtures of chiral, O-substituted diolphosphorus ligands derived from carbohydrates, such as D-glucose, have been used previously as ligands in the catalytic, enantioselective hydrogenation of .alpha.,.beta.-unsaturated acid derivatives. The catalyst compositions of the instant invention, however, which comprise nickel, are not known in the enantioselective hydrocyanation of alkenes.
In addition, the preparation of racemic 2-(6-methoxy-2-naphthalene)propionitrile has been previously reported in Synthetic Commun. 1984, 14, 1365; J. Org. Chem. 1985, 50, 5370, but the preparation of the pure S enantiomer is not disclosed. Using a preferred embodiment of the process of the invention Applicants have achieved the preparation of optically pure (S)-(-)-2-(6-methoxy-2-naphthalene)propionitrile.